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Molecular platform for design and synthesis of targeted dual-modality imaging probes.


ABSTRACT: We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N',N?-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of (68/67)Ga(3+) and Gd(3+), respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM(-1) s(-1) at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with (67)Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection.

SUBMITTER: Kumar A 

PROVIDER: S-EPMC4428032 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Molecular platform for design and synthesis of targeted dual-modality imaging probes.

Kumar Amit A   Zhang Shanrong S   Hao Guiyang G   Hassan Gedaa G   Ramezani Saleh S   Sagiyama Koji K   Lo Su-Tang ST   Takahashi Masaya M   Sherry A Dean AD   Öz Orhan K OK   Kovacs Zoltan Z   Sun Xiankai X  

Bioconjugate chemistry 20150220 3


We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of (68/67)Ga(3+) and Gd(3+), respectively, into a common molecular scaffold. The platform also contains thr  ...[more]

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